Chronic inhibition of cGMP phosphodiesterase 5A improves diabetic cardiomyopathy: A randomized, controlled clinical trial using magnetic resonance imaging with myocardial tagging

Circulation

Volumn 125, Issue 19, 2012, Pages 2323-2333

  Giannetta, Elisa ^a   Isidori, Andrea M ^a   Galea, Nicola ^b   Carbone, Iacopo ^b   Mandosi, Elisabetta ^b   Vizza, Carmine D ^b   Naro, Fabio ^b   Morano, Susanna ^b   Fedele, Francesco ^b   Lenzi, Andrea ^a  

^a SAPIENZA UNIVERSITY OF ROME   (Italy)

^b SAPIENZA UNIVERSITY OF ROME   (Italy)

Author keywords

cardiac magnetic resonance imaging; diabetes mellitus type 2; diabetic diastolic heart failure; fibrosis; phosphodiesterase inhibitors heart failure

Indexed keywords

AMINO TERMINAL PRO BRAIN NATRIURETIC PEPTIDE; ANGIOTENSIN 1 RECEPTOR ANTAGONIST; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; CALCIUM CHANNEL BLOCKING AGENT; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; DIURETIC AGENT; GROWTH HORMONE SECRETAGOGUE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; METFORMIN; MONOCYTE CHEMOTACTIC PROTEIN 1; PLACEBO; SILDENAFIL; TRANSFORMING GROWTH FACTOR BETA; VASCULOTROPIN;

ABSENCE OF SIDE EFFECTS; ADULT; AGED; ARTICLE; BLOOD PRESSURE; CARDIOVASCULAR MAGNETIC RESONANCE; CLINICAL ARTICLE; CONTROLLED STUDY; DIABETIC CARDIOMYOPATHY; DOUBLE BLIND PROCEDURE; DRUG WITHDRAWAL; ENDOTHELIUM; HEART AFTERLOAD; HEART LEFT VENTRICLE CONTRACTION; HEART LEFT VENTRICLE MASS; HEART LEFT VENTRICLE VOLUME; HEART MUSCLE METABOLISM; HUMAN; MALE; NON INSULIN DEPENDENT DIABETES MELLITUS; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL;

AGED; CARDIAC IMAGING TECHNIQUES; CYCLIC NUCLEOTIDE PHOSPHODIESTERASES, TYPE 5; DIABETES MELLITUS, TYPE 2; DIABETIC CARDIOMYOPATHIES; FOLLOW-UP STUDIES; HUMANS; HYPERTROPHY, LEFT VENTRICULAR; MAGNETIC RESONANCE IMAGING; MALE; MIDDLE AGED; PHOSPHODIESTERASE 5 INHIBITORS; PIPERAZINES; PURINES; SULFONES; TORSION, MECHANICAL; TREATMENT OUTCOME; VENTRICULAR REMODELING;

EID: 84861234413     PISSN: 00097322     EISSN: 15244539     Source Type: Journal    
DOI: 10.1161/CIRCULATIONAHA.111.063412     Document Type: Article

References (50)

1. Tsai EJ, Kass DA. Cyclic GMP signaling in cardiovascular pathophysiology and therapeutics. Pharmacol Ther. 2009;122:216-238.
2. Takimoto E, Champion HC, Belardi D, Moslehi J, Mongillo M, Mergia E, Montrose DC, Isoda T, Aufiero K, Zaccolo M, Dostmann WR, Smith CJ, Kass DA. cGMP catabolism by phosphodiesterase 5A regulates cardiac adrenergic stimulation by NOS3-dependent mechanism. Circ Res. 2005;96:100-109. (Pubitemid 40095759)
3. Takimoto E, Champion HC, Li M, Belardi D, Ren S, Rodriguez ER, Bedja D, Gabrielson KL, Wang Y, Kass DA. Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy. Nat Med. 2005;11:214-222. (Pubitemid 40321358)
4. Zhang M, Koitabashi N, Nagayama T, Rambaran R, Feng N, Takimoto E, Koenke T, O'Rourke B, Champion HC, Crow MT, Kass DA. Expression, activity, and pro-hypertrophic effects of PDE5A in cardiac myocytes. Cell Signal. 2008;20:2231-2236.
5. Kumar P, Francis GS, Tang WH. Phosphodiesterase 5 inhibition in heart failure: mechanisms and clinical implications. Nat Rev Cardiol. 2009;6: 349-355.
6. Nagayama T, Hsu S, Zhang M, Koitabashi N, Bedja D, Gabrielson KL, Takimoto E, Kass DA. Sildenafil stops progressive chamber, cellular, and molecular remodeling and improves calcium handling and function in hearts with pre-existing advanced hypertrophy caused by pressure overload. J Am Coll Cardiol. 2009;53:207-215.
7. Salloum F, Yin C, Xi L, Kukreja RC. Sildenafil induces delayed preconditioning through inducible nitric oxide synthase-dependent pathway in mouse heart. Circ Res. 2003;92:595-597. (Pubitemid 36417692)
8. Fisher PW, Salloum F, Das A, Hyder H, Kukreja RC. Phosphodiesterase-5 inhibition with sildenafil attenuates cardiomyocyte apoptosis and left ventricular dysfunction in a chronic model of doxorubicin cardiotoxicity. Circulation. 2005;111:1601-1610. (Pubitemid 40525159)
9. Ferreira-Melo SE, Yugar-Toledo JC, Coelho OR, De Luca IM, Tanus-Santos JE, Hyslop S, Irigoyen MC, Moreno H Jr. Sildenafil reduces cardiovascular remodeling associated with hypertensive cardiomyopathy in NOS inhibitor-treated rats. Eur J Pharmacol. 2006;542:141-147. (Pubitemid 44066358)
10. Rossoni G, Manfredi B, De Gennaro Colonna V, Berti M, Guazzi M, Berti F. Sildenafil reduces L-NAME-induced severe hypertension and worsening of myocardial ischaemia-reperfusion damage in the rat. Br J Pharmacol. 2007;150:567-576. (Pubitemid 46355556)
11. Nagendran J, Archer SL, Soliman D, Gurtu V, Moudgil R, Haromy A, St Aubin C, Webster L, Rebeyka IM, Ross DB, Light PE, Dyck JR, Michelakis ED. Phosphodiesterase type 5 is highly expressed in the hypertrophied human right ventricle, and acute inhibition of phosphodiesterase type 5 improves contractility. Circulation. 2007;116:238-248. (Pubitemid 47196559)
12. Guazzi M, Vicenzi M, Arena R, Guazzi MD. PDE5 inhibition with sildenafil improves left ventricular diastolic function, cardiac geometry, and clinical status in patients with stable systolic heart failure: results of a 1-year, prospective, randomized, placebo-controlled study. Circ Heart Fail. 2011;4:8-17.
13. Voulgari C, Papadogiannis D, Tentolouris N. Diabetic cardiomyopathy: from the pathophysiology of the cardiac myocytes to current diagnosis and management strategies. Vasc Health Risk Manag. 2010;6:883-903.
14. Fonseca CG, Dissanayake AM, Doughty RN, Whalley GA, Gamble GD, Cowan BR, Occleshaw CJ, Young AA. Three-dimensional assessment of left ventricular systolic strain in patients with type 2 diabetes mellitus, diastolic dysfunction, and normal ejection fraction. Am J Cardiol. 2004; 94:1391-1395. (Pubitemid 39556208)
15. Feng B, Chen S, Chiu J, George B, Chakrabarti S. Regulation of cardiomyocyte hypertrophy in diabetes at the transcriptional level. Am J Physiol. 2008;294:E1119-E1126.
16. Dong SJ, Hees PS, Siu CO, Weiss JL, Shapiro EP. MRI assessment of LV relaxation by untwisting rate: a new isovolumic phase measure of tau. Am J Physiol. 2001;281:H2002-H2009.
17. Biederman RW, Doyle M, Yamrozik J, Williams RB, Rathi VK, Vido D, Caruppannan K, Osman N, Bress V, Rayarao G, Biederman CM, Mankad S, Magovern JA, Reichek N. Physiologic compensation is supranormal in compensated aortic stenosis: does it return to normal after aortic valve replacement or is it blunted by coexistent coronary artery disease? An intramyocardial magnetic resonance imaging study. Circulation. 2005; 112:I429-I436. (Pubitemid 41266710)
18. Hundley WG, Bluemke DA, Finn JP, Flamm SD, Fogel MA, Friedrich MG, Ho VB, Jerosch-Herold M, Kramer CM, Manning WJ, Patel M, Pohost GM, Stillman AE, White RD, Woodard PK. ACCF/ACR/AHA/NASCI/SCMR 2010 expert consensus document on cardiovascular magnetic resonance: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents. J Am Coll Cardiol. 2010;55:2614-2662.
19. Hees PS, Fleg JL, Dong SJ, Shapiro EP. MRI and echocardiographic assessment of the diastolic dysfunction of normal aging: altered LV pressure decline or load? Am J Physiol. 2004;286:H782-H788. (Pubitemid 38140362)
20. Thompson RB, Paterson I, Chow K, Cheng-Baron J, Scott JM, Esch BT, Ennis DB, Haykowsky MJ. Characterization of the relationship between systolic shear strain and early diastolic shear strain rates: insights into torsional recoil. Am J Physiol. 2010;299:H898-H907.
21. Esposito K, Ciotola M, Maiorino MI, Giugliano F, Autorino R, De SM, Jannini E, Lenzi A, Giugliano D. Circulating CD34 KDR endothelial progenitor cells correlate with erectile function and endothelial function in overweight men. J Sex Med. 2009;6:107-114.
22. Sandstede JJ, Johnson T, Harre K, Beer M, Hofmann S, Pabst T, Kenn W, Voelker W, Neubauer S, Hahn D. Cardiac systolic rotation and contraction before and after valve replacement for aortic stenosis: a myocardial tagging study using MR imaging. AJR Am J Roentgenol. 2002; 178:953-958. (Pubitemid 34250238)
23. Asghar O, Al-Sunni A, Khavandi K, Khavandi A, Withers S, Greenstein A, Heagerty AM, Malik RA. Diabetic cardiomyopathy. Clin Sci (Lond). 2009;116:741-760.
24. Connelly KA, Kelly DJ, Zhang Y, Prior DL, Martin J, Cox AJ, Thai K, Feneley MP, Tsoporis J, White KE, Krum H, Gilbert RE. Functional, structural and molecular aspects of diastolic heart failure in the diabetic (mRen-2)27 rat. Cardiovasc Res. 2007;76:280-291. (Pubitemid 350214455)
25. Khouri MG, Peshock RM, Ayers CR, de Lemos JA, Drazner MH. A 4-tiered classification of left ventricular hypertrophy based on left ven-tricular geometry: the Dallas Heart Study. Circ Cardiovasc Imaging. 2010;3:164-171.
26. Chung J, Abraszewski P, Yu X, Liu W, Krainik AJ, Ashford M, Caruthers SD, McGill JB, Wickline SA. Paradoxical increase in ventricular torsion and systolic torsion rate in type I diabetic patients under tight glycemic control. J Am Coll Cardiol. 2006;47:384-390. (Pubitemid 43063259)
27. Yu CM, Lin H, Yang H, Kong SL, Zhang Q, Lee SW. Progression of systolic abnormalities in patients with "isolated" diastolic heart failure and diastolic dysfunction. Circulation. 2002;105:1195-1201. (Pubitemid 34225820)
28. Fang ZY, Leano R, Marwick TH. Relationship between longitudinal and radial contractility in subclinical diabetic heart disease. Clin Sci (Lond). 2004;106:53-60. (Pubitemid 38091339)
29. Torrent-Guasp F, Buckberg GD, Clemente C, Cox JL, Coghlan HC, Gharib M. The structure and function of the helical heart and its buttress wrapping, I: the normal macroscopic structure of the heart. Semin Thorac Cardiovasc Surg. 2001;13:301-319. (Pubitemid 34110768)
30. Cappelli F, Toncelli L, Cappelli B, De LA, Stefani L, Maffulli N, Galanti G. Adaptative or maladaptative hypertrophy, different spatial distribution of myocardial contraction. Clin Physiol Funct Imaging. 2010;30:6-12.
31. Fang ZY, Schull-Meade R, Leano R, Mottram PM, Prins JB, Marwick TH. Screening for heart disease in diabetic subjects. Am Heart J. 2005; 149:349-354. (Pubitemid 40348547)
32. Zhang M, Kass DA. Phosphodiesterases and cardiac cGMP: evolving roles and controversies. Trends Pharmacol Sci. 2011;32:360-365.
33. Pokreisz P, Vandenwijngaert S, Bito V, Van den Bergh A, Lenaerts I, Busch C, Marsboom G, Gheysens O, Vermeersch P, Biesmans L, Liu X, Gillijns H, Pellens M, Van LA, Buys E, Schoonjans L, Vanhaecke J, Verbeken E, Sipido K, Herijgers P, Bloch KD, Janssens SP. Ventricular phosphodiesterase-5 expression is increased in patients with advanced heart failure and contributes to adverse ventricular remodeling after myocardial infarction in mice. Circulation. 2009;119:408-416.
34. Zhang M, Takimoto E, Hsu S, Lee DI, Nagayama T, Danner T, Koitabashi N, Barth AS, Bedja D, Gabrielson KL, Wang Y, Kass DA. Myocardial remodeling is controlled by myocyte-targeted gene regulation of phosphodiesterase type 5. J Am Coll Cardiol. 2010;56:2021-2030.
35. Stirban A, Laude D, Elghozi JL, Sander D, Agelink MW, Hilz MJ, Ziegler D. Acute effects of sildenafil on flow mediated dilatation and cardiovascular autonomic nerve function in type 2 diabetic patients. Diabetes Metab Res Rev. 2009;25:136-143.
36. Oliver JJ, Melville VP, Webb DJ. Effect of regular phosphodiesterase type 5 inhibition in hypertension. Hypertension. 2006;48:622-627. (Pubitemid 44843865)
37. Koitabashi N, Danner T, Zaiman AL, Pinto YM, Rowell J, Mankowski J, Zhang D, Nakamura T, Takimoto E, Kass DA. Pivotal role of cardiomyocyte TGF-beta signaling in the murine pathological response to sustained pressure overload. J Clin Invest. 2011;121:2301-2312.
38. Opie LH, Commerford PJ, Gersh BJ, Pfeffer MA. Controversies in ventricular remodelling. Lancet. 2006;367:356-367. (Pubitemid 43151469)
39. Seino Y, Ikeda U, Sekiguchi H, Morita M, Konishi K, Kasahara T, Shimada K. Expression of leukocyte chemotactic cytokines in myocardial tissue. Cytokine. 1995;7:301-304.
40. Bishu K, Hamdani N, Mohammed SF, Kruger M, Ohtani T, Ogut O, Brozovich FV, Burnett JC Jr, Linke WA, Redfield MM. Sildenafil and B-type natriuretic peptide acutely phosphorylate titin and improve diastolic distensibility in vivo. Circulation. 2011;124:2882-2891.
41. Saura M, Zaragoza C, Herranz B, Griera M, Diez-Marques L, Rodriguez-Puyol D, Rodriguez-Puyol M. Nitric oxide regulates transforming growth factor-beta signaling in endothelial cells. Circ Res. 2005; 97:1115-1123.
42. Tesch GH, Lim AK. Recent insights into diabetic renal injury from the db/db mouse model of type 2 diabetic nephropathy. Am J Physiol. 2011; 300:F301-F310.
43. Riddle MC. Glycemic control and cardiovascular mortality. Curr Opin Endocrinol Diabetes Obes. 2011;18:104-109.
44. Kimura M, Higashi Y, Hara K, Noma K, Sasaki S, Nakagawa K, Goto C, Oshima T, Yoshizumi M, Chayama K. PDE5 inhibitor sildenafil citrate augments endothelium-dependent vasodilation in smokers. Hypertension. 2003;41:1106-1110. (Pubitemid 36548611)
45. Guazzi M, Samaja M, Arena R, Vicenzi M, Guazzi MD. Long-term use of sildenafil in the therapeutic management of heart failure. J Am Coll Cardiol. 2007;50:2136-2144. (Pubitemid 350117342)
46. Halcox JP, Nour KR, Zalos G, Mincemoyer RA, Waclawiw M, Rivera CE, Willie G, Ellahham S, Quyyumi AA. The effect of sildenafil on human vascular function, platelet activation, and myocardial ischemia. J Am Coll Cardiol. 2002;40:1232-1240.
47. Robinson SD, Ludlam CA, Boon NA, Newby DE. Phosphodiesterase type 5 inhibition does not reverse endothelial dysfunction in patients with coronary heart disease. Heart. 2006;92:170-176. (Pubitemid 43131953)
48. Gori T, Sicuro S, Dragoni S, Donati G, Forconi S, Parker JD. Sildenafil prevents endothelial dysfunction induced by ischemia and reperfusion via opening of adenosine triphosphate-sensitive potassium channels: a human in vivo study. Circulation. 2005;111:742-746. (Pubitemid 40250634)
49. Desouza C, Parulkar A, Lumpkin D, Akers D, Fonseca VA. Acute and prolonged effects of sildenafil on brachial artery flow-mediated dilatation in type 2 diabetes. Diabetes Care. 2002;25:1336-1339. (Pubitemid 41071142)
50. Vlachopoulos C, Tsekoura D, Alexopoulos N, Panagiotakos D, Aznaouridis K, Stefanadis C. Type 5 phosphodiesterase inhibition by sildenafil abrogates acute smoking-induced endothelial dysfunction. Am J Hypertens. 2004;17:1040-1044. (Pubitemid 39469327)